IGF1R variants associated with isolated single suture craniosynostosis
Michael L Cunningham1, Jeremy A Horst, Mark J Rieder
1Seattle Children's Hospital Craniofacial Center, University of Washington, 98195, USA. mcunning@uw.edu
American Journal of Medical Genetics. Part A
|January 5, 2011
Summary
Genetic variants in the insulin-like growth factor I receptor (IGF1R) gene are linked to isolated single suture craniosynostosis. These IGF1R mutations may increase the risk or cause this condition.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- The genetic basis of isolated single suture craniosynostosis remains largely unknown.
- Known genes associated with syndromic craniosynostosis have limited roles in isolated forms.
Purpose of the Study:
- To identify rare genetic variants contributing to isolated non-syndromic single suture craniosynostosis.
- To investigate the role of candidate genes in the pathogenesis of this condition.
Main Methods:
- Candidate gene resequencing of 27 genes in 186 patients with isolated single suture craniosynostosis.
- Analysis of coding regions, splice sites, and untranslated regions.
- Structural modeling of identified IGF1R variants.
Main Results:
- Three novel and two rare sequence variants in the insulin-like growth factor I receptor (IGF1R) gene were identified.
- These IGF1R variants were enriched in cases compared to controls.
- Structural analysis suggested a basis for disease association of these IGF1R mutations.
Conclusions:
- Mutations in IGF1R are implicated in the pathogenesis of single suture craniosynostosis.
- IGF1R variants may contribute to the risk or causation of this condition.
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